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20  structures 157  species 3  interactions 450  sequences 10  architectures

Family: Synapsin_C (PF02750)

Summary: Synapsin, ATP binding domain

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This is the Wikipedia entry entitled "Synapsin". More...

Synapsin Edit Wikipedia article

Synapsin, N-terminal domain
PDB 1auv EBI.jpg
Structure of the c domain of synapsin IA from bovine brain.[1]
Symbol Synapsin
Pfam PF02078
InterPro IPR001359
SCOP 1auv
OPM superfamily 131
OPM protein 1auv
Synapsin, ATP binding domain
Symbol Synapsin_C
Pfam PF02750
InterPro IPR001359
SCOP 1auv

The synapsins are a family of proteins that have long been implicated in the regulation of neurotransmitter release at synapses. Specifically, they are thought to be involved in regulating the number of synaptic vesicles available for release via exocytosis at any one time.[2]Synapsins are present in invertebrates and vertebrates and are somewhat homologous across evaluated vertebrates.

Current studies suggest the following hypothesis for the role of synapsin: synapsins bind synaptic vesicles to components of the cytoskeleton which prevents them from migrating to the presynaptic membrane and releasing transmitter. During an action potential, synapsins are phosphorylated by PKA (cAMP dependent protein kinase), releasing the synaptic vesicles and allowing them to move to the membrane and release their neurotransmitter.

Gene knockout studies in mice (where the mouse is unable to produce synapsin) have had some surprising results. Mice lacking all three synapsins are prone to seizures, and experience learning defects.[3] These results suggest that while synapsins are not essential for synaptic function, they do serve an important modulatory role. Conversely, studies using transgenic mice in which neuronal signaling is abolished in specific circuitries showed that synaptic activity regulates, but is not essential to maintain, the expression of these proteins.[4]

Family members[edit]

Humans and most other vertebrates possess three genes encoding three different synapsin proteins.[5] Each gene in turn is alternatively spliced to produce at least two different protein isoforms for a total of six isoforms:[6]

Gene Protein Isoforms
SYN1 Synapsin I Ia, Ib
SYN2 Synapsin II IIa, IIb
SYN3 Synapsin III IIIa, IIIb

Different neuron terminals will express varying amounts of each of these synapsin proteins and collectively these synapsins will comprise 1% of the total expressed protein at any one time.[7] Synapsin Ia has been implicated in bipolar disorder and schizophrenia.[8]


  1. ^ Esser L, Wang CR, Hosaka M, Smagula CS, Südhof TC, Deisenhofer J (February 1998). "Synapsin I is structurally similar to ATP-utilizing enzymes". EMBO J. 17 (4): 977–84. doi:10.1093/emboj/17.4.977. PMC 1170447. PMID 9463376. 
  2. ^ Evergren E, Benfenati F, Shupliakov O (September 2007). "The synapsin cycle: a view from the synaptic endocytic zone". J. Neurosci. Res. 85 (12): 2648–56. doi:10.1002/jnr.21176. PMID 17455288. 
  3. ^ Rosahl TW, Geppert M, Spillane D, Herz J, Hammer RE, Malenka RC, Sudhof TC (1993). "Short-term synaptic plasticity is altered in mice lacking synapsin I". Cell 75 (4): 661–670. doi:10.1016/0092-8674(93)90487-B. PMID 7902212. 
  4. ^ Kihara AH, Santos TO, Paschon V, Matos RJ, Britto LR (2008). "Lack of photoreceptor signaling alters the expression of specific synaptic proteins in the retina". Neuroscience 151 (4): 995–1005. doi:10.1016/j.neuroscience.2007.09.088. PMID 18248909. 
  5. ^ Kao HT, Porton B, Hilfiker S, Stefani G, Pieribone VA, DeSalle R, Greengard P (December 1999). "Molecular evolution of the synapsin gene family". J. Exp. Zool. 285 (4): 360–77. doi:10.1002/(SICI)1097-010X(19991215)285:4<360::AID-JEZ4>3.0.CO;2-3. PMID 10578110. 
  6. ^ Gitler D, Xu Y, Kao HT, Lin D, Lim S, Feng J, Greengard P, Augustine GJ (April 2004). "Molecular determinants of synapsin targeting to presynaptic terminals". J. Neurosci. 24 (14): 3711–20. doi:10.1523/JNEUROSCI.5225-03.2004. PMID 15071120. 
  7. ^ Ferreira A, Rapoport M (April 2002). "The synapsins: beyond the regulation of neurotransmitter release". Cell. Mol. Life Sci. 59 (4): 589–95. doi:10.1007/s00018-002-8451-5. PMID 12022468. 
  8. ^ Vawter, MP et al (April 2002). "Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia". Mol. Psychiatry 7 (6): 571–8. doi:10.1038/ PMID 12140780. 

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Synapsin, ATP binding domain Provide feedback

Ca dependent ATP binding in this ATP grasp fold. Function unknown.

Literature references

  1. Esser L, Wang CR, Hosaka M, Smagula CS, Sudhof TC, Deisenhofer J; , EMBO J 1998;17:977-984.: Synapsin I is structurally similar to ATP-utilizing enzymes. PUBMED:9463376 EPMC:9463376

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR020898

The synapsins are a family of neuron-specific phosphoproteins that coat synaptic vesicles and are involved in the binding between these vesicles and the cytoskeleton (including actin filaments). The family comprises 5 homologous proteins Ia, Ib, IIa, IIb and III. Synapsins I, II, and III are encoded by 3 different genes. The a and b isoforms of synapsin I and II are splice variants of the primary transcripts [PUBMED:10940454].

Synapsin I is mainly associated with regulation of neurotransmitter release from presynaptic neuron terminals [PUBMED:2859595]. Synapsin II, as well as being involved in neurotransmitter release, has a role in the synaptogenesis and synaptic plasticity responsible for long term potentiation [PUBMED:7777057]. Recent studies implicate synapsin III with a developmental role in neurite elongation and synapse formation that is distinct from the functions of synapsins I and II [PUBMED:10804215].

Structurally, synapsins are multidomain proteins, of which 3 domains are common to all the mammalian forms. The N-terminal `A' domain is ~30 residues long and contains a serine residue that serves as an acceptor site for protein kinase-mediated phosphorylation. This is followed by the `B' linker domain, which is ~80 residues long and is relatively poorly conserved. Domain `C' is the longest, spanning approximately 300 residues. This domain is highly conserved across all the synapsins (including those from Drosophila) and is possessed by all splice variants. The remaining six domains, D-I, are not shared by all the synapsins and differ both between the primary transcripts and the splice variants.

This entry represent the ATP-grasp fold found in synapsins, which is responsible for Ca dependent ATP binding.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan ATP-grasp (CL0179), which has the following description:

The ATP-grasp domain is found in a wide variety of carboxylate-amine/thiol ligases [1]. It is composed of two subdomains, with ATP being bound in the cleft between the two.

The clan contains the following 21 members:

ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_TupA ATPgrasp_YheCD CP_ATPgrasp_1 CP_ATPgrasp_2 CPSase_L_D2 Dala_Dala_lig_C DUF1297 GARS_A GSH-S_ATP GSP_synth Ins134_P3_kin RimK Synapsin_C TTL


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Curation and family details

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Seed source: IPR001359
Previous IDs: none
Type: Domain
Author: Mian N, Bateman A, Griffiths-Jones SR
Number in seed: 2
Number in full: 450
Average length of the domain: 165.10 aa
Average identity of full alignment: 55 %
Average coverage of the sequence by the domain: 36.79 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.5 22.5
Trusted cut-off 22.5 22.5
Noise cut-off 22.4 22.2
Model length: 203
Family (HMM) version: 10
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Species distribution

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There are 3 interactions for this family. More...

Synapsin Synapsin_C Synapsin


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Synapsin_C domain has been found. There are 20 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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